Antiretroviral therapy (ART) has enormous benefits for HIV-infected persons, including improved morbidity and mortality and reduced secondary transmissions. In sub-Saharan Africa, rapid scale-up of ART has allowed over four million persons to receive therapy. Maximizing treatment outcomes in these persons requires sufficient adherence and appropriate regimen selection. Viral load (VL) monitoring is one approach that has been underutilized in Africa, but has the potential to enhance long-term outcomes. Expanded monitoring may be critical to improving adherence, maintaining treatment efficacy, preserving therapeutic options, and controlling emerging resistant strains. Behaviorally, VL monitoring may be a potent motivator to improve adherence. The VL communicates important information to the patient regarding the threat of increasing severity of disease. Knowledge of an increased VL is a warning sign that may improve a patient's adherence behavior. For persons with resistance mutations, simple algorithms are needed to guide decisions and ensure prompt conversion to second-line therapy to minimize poor outcomes and transmission of resistant virus. Cost-effective interventions to maximize ART effects must consider the role of adherence and resistance in driving outcomes. Comprehensive cost-effectiveness analyses provide insight for policymakers considering implementation of monitoring strategies, addressing the consequences of early initiation of ART on a larger scale. The overall objective of this Kirschstein-NRSA individual fellowship (F30) proposal is to identify the clinical and policy implications of VL monitoring in sub-Saharan Africa, facilitating the development of sustainable, cost-effective ART monitoring to maximize treatment outcomes. The specific aims of this proposal are: 1) To evaluate the effect of providing VL information on ART adherence; 2) To develop a predictive model to identify persons with resistance from a single elevated VL; and 3) To develop a generalizable cost-effectiveness model to a) compare point-of-care, DBS, and conventional VL monitoring to current standard of care, and b) conduct optimization evaluation for design and pricing of forthcoming point-of-care tests. The proposed research includes an ancillary study of a prospective cohort study designed to examine the effect of VL information on ART adherence (Aim 1); a retrospective analysis of RCT data to improve efficiency in identifying treatment failure (Aim 2); and a generalizable cost-effectiveness analysis to inform VL monitoring policy (Aim 3). Through this research project and a carefully constructed training plan, the trainee will achieve the following fellowship goals: 1) develop advanced skills in econometric, clinical, and behavioral research methods; 2) acquire clinical and translational research skills; and 3) develop professional skills necessary to foster a successful academic career. PUBLIC HEALTH RELEVANCE: Maximizing the potential benefits of HIV medicine is critical to improve long-term outcomes for HIV-infected patients on treatment. Monitoring the amount of virus in an HIV patient's blood provides vital information about a person's response to therapy, but only a fraction of the four million persons on HIV treatment in sub-Saharan Africa have routine monitoring. This study will evaluate the impact of viral monitoring on adherence to HIV medicines in sub-Saharan Africa and examine the cost-effectiveness of widespread implementation to inform evidence-based HIV-therapy monitoring guidelines in sub-Saharan Africa.